Intraperitoneal Chemotherapy Improves Survival in Ovarian Cancer Patients With Low BRCA1 Levels

Jamie Lesnock, MD

Patients with epithelial ovarian cancer (EOC) and low levels of the BRCA1 protein had significantly improved overall survival (OS) when their platinum-based chemotherapy was delivered abdominally by injection, according to findings of a Gynecologic Oncology Group (GOG) study published online in the British Journal of Cancer.

GOG-172 was a multi-institutional, randomized phase III trial of intravenous (IV) versus intraperitoneal (IP) chemotherapy in patients with EOC or primary peritoneal cancer (PPC). No test is currently available to determine which patients may benefit from the more aggressive IP regimens, though a number of phase III trials have shown a survival advantage when this route is used for patients with advanced EOC.

For this analysis, archival tissues were analyzed from 393 patients with stage III EOC or PPC, representing 95% of the clinical trial’s participants. BRCA1 expression in the tumor samples was assessed using immunohistochemistry (IHC). Forty-eight percent of the samples (n = 189) had aberrant (low or absent) BRCA1 expression, and 52% had normal expression (n = 204).

OS was similar between the two groups when route of administration was not factored in. However, when the treatment regimen was taken into account, researchers found a statistically significant correlation between tumor expression of BRCA1 and route of administration, most notable in the aberrant group, which had the best results when receiving IP chemotherapy.

Patients with aberrant BRCA1 expression receiving IP chemotherapy had a median OS of 84 months, versus 48 months in those with aberrant expression who received their chemotherapy intravenously (P = .0002), representing a 3-year survival advantage. For patients with normal BRCA1 expression receiving IP or IV chemotherapy, median OS was 58 months and 50 months, respectively (P = .818). Median progression-free survival was 35 months in the aberrant BRCA1/IP group, compared with <20 months in the other three subgroups.

The researchers noted that the prognostic value of aberrant BRCA1 expression was independent of other factors, such as the patient’s age, microscopic versus gross residual disease, and histologic subtype.

“Our findings suggest that IHC assessment of BRCA1 expression should be prospectively studied as a guide for the decision to use chemotherapy,” said the study’s lead author, Jamie Lesnock, MD, and coauthors. Lesnock is in the Division of Gynecologic Oncology at the Magee-Women’s Hospital at the University of Pittsburgh Medical Center in Pennsylvania. “The significant survival advantage in patients with aberrant BRCA1 expression treated with IP chemotherapy suggests that we can make a substantial improvement in this specific group of patients.”

If the study results are confirmed, another potential advantage would be that patients with normal BRCA1 expression could be spared the more severe side effects associated with IP therapy, the researchers noted.

The National Cancer Institute estimates that 22,240 new cases of EOC will be diagnosed in 2013 and that 14,030 women will die of the disease.

Lesnock JL, Darcy KM, Tian C, et al. BRCA1 expression and improved survival in ovarian cancer patients treated with intraperitoneal cisplation and paclitaxel: a Gynecologic Oncology Group study [published online ahead of print March 5, 2013]. Br J Cancer. doi: 10.1038/bjc.2013.70.